College of LAS « Illinois

Cover Story

A Race to the Bottom: Nanodiscs

A ‘wild idea’ opens the doors of drug discovery.

“People thought we were nuts,” says Stephen Sligar, when they first came up with the idea of a nanodisc.

A nanodisc is a 10-nanometer-long slice of cell membrane, stabilized by a protein that encircles it like a disc, says Sligar, an LAS biochemistry professor. To get a grasp of just how small these dimensions are, a typical virus is three to five times larger than the membrane found at the heart of a nanodisc. But today this small device is making big waves in the scientific community, especially when it comes to those elusive membrane proteins, which play a key role in drug development.

According to Sligar, more than half of the pharmaceutical drugs on the market today target proteins within cell membranes. Nevertheless, most of the membrane proteins out there have not been tapped as drug targets for one important reason.

“Membrane proteins are extremely difficult to study because if you remove them from the cell membrane, they become inactive, they aggregate like scrambled eggs, and they die,” he says.

Enter nanotechnology.

Banking on what Sligar describes as “a wild idea,” his lab developed nanodiscs to fool the proteins into thinking that they are still inside a typical cell membrane within the human body.

“The membrane protein remains active in a nanodisc and can be studied much more effectively,” he points out.

By making it easier to study membrane proteins, nanodiscs allow researchers to probe the vast number of possible pharmaceutical targets. Sligar’s nanodiscs have also been used to create images of important biological processes, such as the first-ever picture of a newly born protein moving out of a ribosome and into a cell membrane, as well as images that show how blood-clotting proteins bind with cell membranes. Nanodiscs even have the potential to be used to deliver therapeutic treatments directly to cancer cells. With this much versatility, the U of I has been actively licensing the technology for all kinds of uses.

Like many other nano devices, nanodiscs are created when small particles “self-assemble,” which is when isolated components come together to form organized structures. By manipulating certain chemical reactions, a nanostructure essentially builds itself at the molecular level.

According to Sligar, people were skeptical about nanodiscs at first, and they wondered, “How could this work?” But as he puts it, “Today some of the most important chemists studying self-assembly say that nanodiscs are the best example of self-assembly they know.”